Individualized Radiation Dose Prescription in HNSCC Based on F-MISO-PET Hypoxia-Imaging (INDIRA-MISO)

Technische Universität Dresden

Status and phase: Not yet enrolling; Phase 2

Conditions: Head and Neck Squamous Cell Carcinoma

Treatments: Radiation: dose-escalated radiochemotherapy with carbon ion boost; Radiation: standard radiochemotherapy; Radiation: dose-escalated radiochemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT03865277

STR-INDIRA-MISO-2014

Details and patient eligibility

About

The trial evaluates the value of radiation dose escalation based on Hypoxia detection by 18F_misonidazole Positron Emission Tomography (18F-MISO-PET) for primary radiochemotherapy of head and neck squamous cell carcinoma. Patients negative for human papillomavirus (HPV) and with hypoxic tumours after 2 weeks of radiochemotherapy are randomized to completion of standard radiochemotherapy or radiochemotherapy with escalated radiation dose. An additional interventional arm includes a carbon ion boost. HPV positive tumours can be included in a control arm. Primary endpoint is local tumour control 2 years after radiochemotherapy.

Full description

Previous preclinical data and a prospective validated patient cohort have shown that patients with head and neck squamous cell carcinoma, whose tumours are hypoxic after 2 weeks of primary radiochmeotherapy, have a significantly lower chance of locoregional tumour control. The multi-center trial evaluates the value of radiation dose escalation based on hypoxia detection by 18F_misonidazole Positron Emission Tomography (18F-MISO-PET) for primary radiochemotherapy of head and neck squamous cell carcinoma. Patients negative for human papillomavirus (HPV) and with hypoxic tumours after 2 weeks of radiochemotherapy are randomized to completion of standard radiochemotherapy (70 Gy) or radiochemotherapy with escalated radiation dose (77 Gy). An additional interventional arm includes a carbon ion boost to 77 Gy. HPV positive tumours can be included in a control arm. Primary endpoint is local tumour control 2 years after radiochemotherapy. Secondary endpoints include acute and late toxicity (CTCAE 5.0), regional tumor control, overall survival, disease free survival, distant metastases, kinetics analysis of dynamic FMISO-PET scans, Quality of life (QoL). The hypothesis is that local tumour control 2 years after radiochemotherapy is higher in the dose escalated compared to the control arm.

Enrollment: 276 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age: older than 18 years
• WHO (ECOG) performance status 0-2
• Histological proven HNSCC
• HPV negative tumors or HPV positive tumors
• Stage III, IVA or IVB HNSCC according to UICC and AJCC guidelines
• Tumor classified as irresectable or patient inoperable or patient refused surgery
• Tumor extension and localization suitable for radiochemotherapy with curative intent
• Simultaneous standard chemotherapy with cisplatin applicable (no contra-indications)
• Dental examination and -treatment before start of therapy
• For women with childbearing potential and men in reproductive ages adequate contraception.
• Ability of subject to understand character and individual consequences of the clinical trial
• Written informed consent (must be available before enrolment in the trial)

Exclusion criteria

• Refusal of the patients to take part in the trial
• Presence of distant metastases (UICC stage IVC)
• Previous radiotherapy in the head and neck region
• Second malignancy that is likely to require treatment during the trial intervention or follow-up period or that, in the opinion of the physician, has a considerable risk of recurrence or metastases within the follow-up period
• Serious disease or medical condition with life expectancy of less than one year
• Participation in competing interventional trial on cancer treatment
• Patients who are not suitable for radiochemotherapy
• Pregnant or lactating women
• Patients not able to understand the character and individual consequences of the trial
• Nasopharyngeal Carcinomas

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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276 participants in 5 patient groups

standard radiochemotherapy, hypoxic

Other group

Description:

HPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, randomized to standard radiation dose, 70 Gy standard radiochemotherapy

Treatment:

Radiation: standard radiochemotherapy

dose-escalated radiochemotherapy, hypoxic

Experimental group

Description:

HPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, randomized to escalated radiation dose, 77 Gy radiochemotherapy

Treatment:

Radiation: dose-escalated radiochemotherapy

escalated radiochemoth., carbon boost, hypoxic

Experimental group

Description:

HPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, non-randomised arm (only possible in the trial center Heidelberg), 77 Gy radiochemotherapy (boost with carbon)

Treatment:

Radiation: dose-escalated radiochemotherapy with carbon ion boost

standard radiochemotherapy, oxic

Other group

Description:

HPV (-), oxic in 18F-MISO PET after 2 weeks of radiochemotherapy, 70 Gy standard radiochemotherapy

Treatment:

Radiation: standard radiochemotherapy

standard radiochemotherapy (70 Gy)

Other group

Description:

HPV (+), HPV positive patients will get the same imaging and clinical examinations as HPV negative patients. This measure is necessary to further elucidate the prognostic role of hypoxia and HPV status and their correlation, the information will be important for consecutive clinical trials. 70 Gy standard radiochemotherapy.

Treatment:

Radiation: standard radiochemotherapy